Comparing somatic mutation-callers: beyond Venn diagrams

Abstract

BACKGROUND: Somatic mutation-calling based on DNA from matched tumor-normal patient samples is one of the key tasks carried by many cancer genome projects. One such large-scale project is The Cancer Genome Atlas (TCGA), which is now routinely compiling catalogs of somatic mutations from hundreds of paired tumor-normal DNA exome-sequence data. Nonetheless, mutation calling is still very challenging. TCGA benchmark studies revealed that even relatively recent mutation callers from major centers showed substantial discrepancies. Evaluation of the mutation callers or understanding the sources of discrepancies is not straightforward, since for most tumor studies, validation data based on independ..